Long-range Electrostatic Repulsion Research Articles

Statistical Thermodynamic Description of Self-Assembly of Large Inclusions in Biological Membranes.

Recent studies revealed anomalous underscreening in concentrated electrolytes, and we suggest that the underscreened electrostatic forces between membrane proteins play a significant role in the process of self-assembly. In this work, we assumed that the underscreened electrostatic forces compete with the thermodynamic Casimir forces induced by concentration fluctuations in the lipid bilayer, and developed a simplified model for a binary mixture of oppositely charged membrane proteins with different preference to liquid-ordered and liquid-disordered domains in the membrane. In the model, like macromolecules interact with short-range Casimir attraction and long-range electrostatic repulsion, and the cross-interaction is of the opposite sign. We determine energetically favored patterns in a system in equilibrium with a bulk reservoir of the macromolecules. Different patterns consisting of clusters and stripes of the two components and of vacancies are energetically favorable for different values of the chemical potentials. Effects of thermal flutuations at low temperature are studied using Monte Carlo simulations in grand canonical and canonical ensembles. For fixed numbers of the macromolecules, a single two-component cluster with a regular pattern coexists with dispersed small one-component clusters, and the number of small clusters depends on the ratio of the numbers of the molecules of the two components. Our results show that the pattern formation is controlled by the shape of the interactions, the density of the proteins, and the proportion of the components.

Microscopically segregated ligand distribution in co-assembled peptide-amphiphile nanofibers.

Peptide amphiphiles (PAs) self-assemble into cylindrical nanofibers with applications in protein purification, tissue engineering, and regenerative medicine. For these applications, functionalized PAs are often co-assembled with oppositely charged filler PAs. Finding the conditions at which these fibers are homogeneously mixed or segregated is crucial for the required application. We co-assemble negative C12VVEE fillers and positive C12VVKK-OEG4-Z33 ligands, which are important for antibody purifications. Our results show that the ligands tend to cluster and locally segregate in the fiber surfaces. The Z33s are overall neutral and form large aggregates in bulk solution due to short range attractions. However, full segregation of the C12VVKK-OEG4-Z33 is not observed in the cylindrical surface due to the electrostatic penalty of forming large domains of similarly charged molecules. This is commensurate with previous theoretical predictions, showing that the competition between short-range attractive interactions and long-range electrostatic repulsions leads to pattern formation in cylindrical surfaces. This work offers valuable insight into the design of functionalized nanofibers for various biomedical and chemical applications.

Improved Diffusion Interaction Parameter Measurement to Predict the Viscosity of Concentrated mAb Solutions.

During the developability assessment of therapeutic monoclonal antibody (mAb) candidates, utilization of robust high-throughput predictive assays enables rapid selection of top candidates with low risks for late-stage development. Predicting the viscosities of highly concentrated mAbs using limited materials is an important aspect of developability assessment because high viscosity can complicate manufacturability, stability, and administration. Here, we report a high-throughput assay measuring protein-protein interactions to predict mAb viscosity. The diffusion interaction parameter (kD) measures colloidal self-association in dilute solutions and has been reported to be predictive of the mAb viscosity at high concentrations. However, kD of Amgen early stage IgG1 mAb candidates measured in 10 mM acetate at pH 5.2 containing sucrose and polysorbate (denoted A52SuT) shows only weak correlation to their viscosities at 140 mg/mL in A52SuT. We hypothesize that kD measured in A52SuT reflects primarily long-range electrostatic repulsions because most of these mAb candidates carry strong net positive charges in this low ionic strength formulation with pH (5.2) well below pI values of mAb candidates. However, the viscosities of high concentration mAbs depend heavily on short-range molecular interactions. We propose an improved kD method in which salt is added to suppress charge repulsions and to allow for detection of key short-range interactions in dilute solutions. Salt types and salt concentrations were screened, and an optimal salt condition was identified. This optimized method was further validated using two test mAb sets. Overall, the method improves the Pearson R2 between kD and viscosity (6-230 cP) from 0.24 to 0.80 for a data set consisting of 37 mAbs.

Subclass Effects on Self-Association and Viscosity of Monoclonal Antibodies at High Concentrations.

The effects of a subclass of monoclonal antibodies (mAbs) on protein-protein interactions, formation of reversible oligomers (clusters), and viscosity (η) are not well understood at high concentrations. Herein, we quantify a short-range anisotropic attraction between the complementarity-determining region (CDR) and CH3 domains (KCDR-CH3) for vedolizumab IgG1, IgG2, or IgG4 subclasses by fitting small-angle X-ray scattering (SAXS) structure factor Seff(q) data with an extensive library of 12-bead coarse-grained (CG) molecular dynamics simulations. The KCDR-CH3 bead attraction strength was isolated from the strength of long-range electrostatic repulsion for the full mAb, which was determined from the theoretical net charge and a scaling parameter ψ to account for solvent accessibility and ion pairing. At low ionic strength (IS), the strongest short-range attraction (KCDR-CH3) and consequently the largest clusters and highest η were observed with IgG1, the subclass with the most positively charged CH3 domain. Furthermore, the trend in KCDR-CH3 with the subclass followed the electrostatic interaction energy between the CDR and CH3 regions calculated with the BioLuminate software using the 3D mAb structure and molecular interaction potentials. Whereas the equilibrium cluster size distributions and fractal dimensions were determined from fits of SAXS with the MD simulations, the degree of cluster rigidity under flow was estimated from the experimental η with a phenomenological model. For the systems with the largest clusters, especially IgG1, the inefficient packing of mAbs in the clusters played the largest role in increasing η, whereas for other systems, the relative contribution from stress produced by the clusters was more significant. The ability to relate η to short-range attraction from SAXS measurements at high concentrations and to theoretical characterization of electrostatic patches on the 3D surface is not only of fundamental interest but also of practical value for mAb discovery, processing, formulation, and subcutaneous delivery.

Probing Colloidal Assembly on Non-Axisymmetric Droplet Surfaces via Electrospray.

Microparticles trapped on the surface of a sessile droplet interact via electrostatic and capillary forces. The assembly of colloids at a fluid-fluid interface is governed by particle size, surface chemistry, and contact line roughness. We created nonspherical droplets using surface energy patterning and delivered microparticles to the liquid-air interface with electrospray atomization. Using a water droplet as the target, the particle assembly was observed over time. We found that the underlying surface energy pattern significantly influenced the colloidal assembly and drove particles toward the center of the droplet. The particles were arranged into a single, non-close-packed cluster with local hexagonal ordering but left a clear region with very few particles near the contact line. This depletion region is attributed to long-range electrostatic repulsion from the photoresist used to create the surface energy pattern, which retained electric charge from the electrospray. To understand the effect of electrostatic interactions, we explored target droplets with dissimilar dielectric properties. Using patterned substrates and electrospray for particle deposition, we can harness the assembly of colloids at a fluid interface to build repeatable monolayer patterns.

Presence, origins and effect of stable surface hydration on regenerated cellulose for underwater oil-repellent membranes

HypothesisUnderwater oil-repellency of polyelectrolyte brushes has been attributed mainly to electric double-layer repulsion forces based on Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Many non-polyelectrolyte materials also exhibit oil-repellent behaviour, but it is not clear if there exist similar electric double-layer repulsion and if it is the sole mechanism governing their underwater oil-repellency. Experiments/simulationsIn this article, the oil-repellency of highly amorphous cellulose exhibiting is investigated in detail, through experiments and molecular dynamics simulations (MDS). FindingsIt was found that the stable surface hydration on regenerated cellulose was due to a combination of long-range electrostatic repulsions (DLVO theory) and short-range interfacial hydrogen bonding between cellulose and water molecules (as revealed by MDS). The presence of a stable water layer of about 200 nm thick (similar to that of polyelectrolyte brushes) was confirmed. Such stable surface hydration effectively separates cellulose surface from oil droplets, resulting in extremely low adhesion between them. As a demonstration of its practicality, regenerated cellulose membranes were fabricated via electrospinning, and they exhibit high oil/water separation efficiencies (including oil-in-water emulsions) as well as self-cleaning ability.

Insight on bulk shear strength parameters of clay using discrete element approach incorporating physics-based interparticle force model

This paper aims to provide insight on factors affecting the bulk shear strength parameters of clay, i.e., the cohesion and internal friction as well as the effects of memory of preconsolidation pressure. A unique Discrete Element Method (DEM) model is built on platy particles with customized particle interaction force model. The particle interaction force model considers non-contact forces (such as the long-range electrostatic repulsion, short-range van der Waals attraction) as well as the direct contact force. The long-range electrostatic forces are calibrated by measurement with Atomic Force Microscope (AFM). Parameters for direct particle contacts of the regular DEM contact model, such as the contact stiffness and the friction coefficient, are calibrated by use of experimental consolidation and direct shear testing data. Computational simulations are conducted on digital clay specimen subjected to virtual direct shear tests. The predicted experimental responses of the digital specimens are consistent with typically observed in experiments including the shear stress-shear strain relationship, volumetric contraction and dilation, shear band formation, etc. From the stress–strain curves, the soil strength parameters are obtained with common experimental criteria. The DEM simulation results show that higher preconsolidation pressure drives more particles to overcome non-contact force into direct contacts and consequently bonding by van der Waals force. Consequently, the bulk cohesion of clay increases with increasing preconsolidation pressure. The results show that bulk cohesion strength is mainly attributed to the attractive interparticle force as well as the interlocking of platy particle, while the bulk internal friction angle is affected by the particle friction coefficient and particle fabric. Overall, the simulation results indicate the experimentally observed macroscopic shear strength parameters c and φ are linked to the microscope characteristics of soil particles and their mutual interactions. The results offer insight on the microscopic properties of particles on the bulk macroscopic strength behaviors. Besides, this work demonstrates a new strategy for simulation-based prediction of bulk soil strength parameters, by incorporating microscale characterization of the interparticle interactions and particle fabric into the particle-based DEM model.

In Situ Assay of Interfacial Interaction between ZnO Nanoparticles and Live Cell Disturbed by Surfactants.

The interfacial interaction between pollutants and organisms is a critical process in controlling the environmental fates of pollutants; however, in situ assay of the interaction is still a great challenge. Here, in situ determination of dissociation constants (Kd) for ZnO nanoparticles (ZnO NPs) from live algal cells disturbed by different-charged surfactants was established using microscale thermophoresis (MST). Moreover, in situ measurement of the adhesion force between the ZnO NPs probe and live single cell was performed using an atomic force microscope (AFM). Results showed that the cationic cetyltrimethylammonium chloride (CTAC) and anionic sodium dodecylbenzenesulfonate (SDBS) increased but nonionic Triton X-100 (TX-100) decreased the adhesion of ZnO NPs on cells. However, the force signature exhibited a smooth single retracted peak at short distances in the SDBS- and TX-100-treated groups, distinguished from the "see-saw" pattern peak in the CTAC-treated groups. The extended Derjaguin-Landau-Verway-Overbeek (XDLVO) calculation further confirmed that SDBS and TX-100 mainly disturbed the short-range hydration on the NP-cell interface, while CTAC reduced the long-range electrostatic repulsion. Furthermore, an excellent linear correlation between Zn bioaccumulation and two parameters (Kd and adhesion force) indicated that NP-cell interfacial interactions affected Zn bioaccumulation. Thus, in situ assay provides a quantitative basis for the pollutant-organism interfacial interaction to evaluate the environmental fate and ecological risk of pollutants.

Coupling between long ranged repulsions and short ranged attractions in a colloidal model of zero shear rate viscosity

In this work, we analyzed an isotropic colloidal model incorporating both short-range sticky attractions and long-range electrostatic repulsions. We computed the zero-shear viscosity and second virial coefficient for a dilute colloidal suspension (i.e., pair interactions only) as a function of the strength of attractions and repulsions. We also developed an analytical approximation that allows us to better understand the coupling of the two types of interactions. The attractions and repulsions contribute to the zero-shear viscosity and second virial coefficient in different ways, leading to cases with the same second virial coefficient but different zero-shear viscosity. The analytical approximation shows that the mechanism of the coupling of interactions is that long-range repulsions can weaken the influence of short-range attractions. This effect alters how repulsions change the zero-shear viscosity. Acting independently, both attractions and repulsions increase the viscosity coefficient of the system. However, when both types of interactions are considered together, repulsions can screen the effect of attractive interactions, thereby reducing the viscosity.

Characterization of hen phosvitin in aqueous salt solutions: Size, structure, and aggregation

Phosvitins is a key egg yolk protein and can often be found in food emulsions. It is highly phosphorylated and hence phosvitins contain a large number of negatively charged amino acid groups, for pH > pI. Due to the presence of these phophoserines, phosvitins bind to positively charged multivalent ions. Its amphipolar structure makes phosvitin also an efficient emulsion stabilizer. The ion binding and emulsifying abilities of phosvitins are influenced by environmental conditions such as pH and ionic strength. Various physicochemical properties of phosvitins such as size and charge under various conditions, and how they self-assemble via multivalent ions are not well-understood. To gain more insight into these physical characteristics, we performed high brilliance synchrotron small angle X-ray scattering (SAXS) on phosvitin solutions. The structure factor S(q) obtained from the SAXS profiles showed that the double layer interactions between charged phosvitin assemblies are strongly affected by pH and ionic strength of the buffer. The effects of multivalent ions (Mg2+, Fe3+) on the size and structure of phosvitin were also investigated. Our results revealed that the aggregation of phosvitin mediated by metal ions is induced by electrostatic attraction and only occurs beyond a threshold cation concentration, where phosvitin loses long-range electrostatic double layer repulsions. These findings help understanding the effects of metal ions and pH on phosvitin in more complex environments such as food emulsions.

Adsorption and interaction forces of commercial Poly(naphthalene sulfonate) (PNS) and Poly(carboxylate ether) (PCE) polyelectrolytes with negatively charged surfaces in monovalent and divalent electrolytes

Adsorption of polyelectrolytes on colloidal particles alters the interaction forces and rheological properties of colloidal suspensions. Poly(naphthalene sulfonate) (PNS) and poly(carboxylate ether) (PCE) polyelectrolytes are commonly added to improve the flowability of hydrated cement paste in low-water conditions. The interactions of commercial PNS and PCE admixtures with negatively charged mica in aqueous electrolytes were directly studied with a surface forces apparatus in this work. In 0.1 M K2SO4, robust adsorption of PNS induced a strong steric repulsion. A slightly thicker adsorption layer formed in low ionic strength 5 mM Ca(NO3)2 exhibiting long-range electrostatic repulsion and short-range steric repulsion. Increasing the Ca(NO3)2 concentration to 0.1 M doubled the adsorption layer thickness and strongly screened any electrostatic repulsion. Contact of the adsorbed PNS layers caused weak physical cohesion under both low and high calcium concentrations presumably due to Ca2+ ion bridging of the opposing PNS layers. These findings indicate that (i) divalent Ca2+ possesses a much stronger ability than monovalent K+ to assemble PNS molecules resulting in significantly thicker adsorption and (ii) the interaction force between PNS adsorption layers in high ionic strength conditions is dominated by steric repulsion. In comparison, PCE did not appreciably adsorb from 0.1 M Ca(NO3)2. This finding challenges the well-accepted divalent ion bridging adsorption mechanism of PCE onto negatively charged surfaces and warrants further study.

Long-Range Electrostatic Colloidal Interactions and Specific Ion Effects in Deep Eutectic Solvents.

While the traditional consensus dictates that high ion concentrations lead to negligible long-range electrostatic interactions, we demonstrate that electrostatic correlations prevail in deep eutectic solvents where intrinsic ion concentrations often surpass 2.5 M. Here we present an investigation of intermicellar interactions in 1:2 choline chloride:glycerol and 1:2 choline bromide:glycerol using small-angle neutron scattering. Our results show that long-range electrostatic repulsions between charged colloidal particles occur in these solvents. Interestingly, micelle morphology and electrostatic interactions are modulated by specific counterion condensation at the micelle interface despite the exceedingly high concentration of the native halide from the solvent. This modulation follows the trends described by the Hofmeister series for specific ion effects. The results are rationalized in terms of predominant ion–ion correlations, which explain the reduction in the effective ionic strength of the continuum and the observed specific ion effects.

Towards thermodynamically stable anionic dimers with “anti-electrostatic” hydrogen bonds overcoming like-charge repulsion

We provide quantum chemical evidence for thermodynamically stable anionic dimers, wherein short-range, attractive hydrogen bonds overcome long-range, repulsive Coulomb interaction. We employed ab initio and density functional theory for studying the kinetic and thermodynamic stability for homodimers of singly deprotonated dicarboxylic acid anions. For the dimeric structures (HOOC(CH2)nCOO−)2 with n = 0–4 we calculated robust local minima with clear dissociation barriers preventing “Coulomb explosion” into separated anions. Already for n = 5 hydrogen bonding and dispersion forces fully compensate for the repulsive Coulomb forces between the anions allowing for the quantification of the two equivalent hydrogen bonds and dispersion interaction in the order of 62 kJmol−1 and 11 kJmol−1 respectively. The increasing kinetic stability even turns into thermodynamic stability with increasing number of methylene groups tethering the negative charges at the carboxylate groups. For n > 5 quantum-type short-range attraction wins over classical long-range electrostatic repulsion resulting in negative binding energies and providing the first energetically stable anionic dimers. For n = 6 and n = 7 we calculated negative free energies below 50 and 100 K, respectively. Even considering pressure effects, the dimers of the singly deprotonated octanedioic acid and nonanedioic acid anions should be detectable by means of cryogenic ion vibrational spectroscopy at temperatures from 10 to 30 K. We rationalize the H-bond characteristics of the dimers by the Natural Bond Orbital (NBO) approach, emphasizing the strong correlation between NBO-based and experimental descriptors.

Fungal spore adhesion on glycidoxypropyltrimethoxy silane modified silica nanoparticle surfaces as revealed by single cell force spectroscopy.

Thin film coatings prepared from commercially available glycidoxypropyltrimethoxysilane (GPS) modified silica nanoparticles (SiNPs) (Bindzil® CC301 and Bindzil® CC302) have previously shown excellent antifouling performance against a broad range of microbes [Molino et al., "Hydration layer structure of biofouling-resistant nanoparticles," ACS Nano 12, 11610 (2018)]. In this work, single cell force spectroscopy (SCFS) was used to measure the biological interactions between Epicoccum nigrum fungal spores and the same silica nanoparticle-based surfaces used in the aforementioned study, including a: glass coverslip, unmodified SiNP coatings, and both low (Bindzil® CC301) and high density (CC302) GPS functionalized SiNP coatings as a function of NaCl concentration. From the SCFS curves, the spore adhesion to the surface was greatest on the glass coverslip (20-80 nN) followed by the unmodified SiNP (3-5 nN) across all salt concentrations. Upon approach to both surfaces, the spores showed a long-range attraction generally with a profile characteristic of biointeractions and likely those of the outer cell wall structures or biological constituents. The attractive force allowed the spores to initially adhere to the surface and was found to be linearly proportional to the spore adhesion. In comparison, both high and low density GPS-SINP significantly reduced the spore adhesion (0.5-0.9 nN). In addition, the spore adhesion on high density GPS-SiNP occurred in only 14%-27% of SCFS curves (40%-48% for low density GPS-SiNP) compared to 83%-97% for the unmodified SiNP, indicating that in most cases the GPS functionalization completely prevented spore adhesion. The GPS-SiNP surfaces conversely showed a long-range electrostatic repulsion at low 1mM NaCl that was replaced by short-range repulsion at the higher salt concentrations. From the findings, it is proposed that the attractive force is a critical step in initial adhesion processes of the spore. The effective antifouling properties of the GPS are attributed to the ability to negate the attractive forces, either through electrostatic repulsion in low salt conditions and primarily from short-range repulsion correlating to the previously reported combined steric-hydration effect of the GPS functionalization on SiNP coatings.

Mechanoresponsive Alignment of Molecular Self-Assembled Negatively Charged Nanofibrils.

Inspired by the mechanoresponsive orientation of actin filaments in cell, we introduce a design paradigm of synthetic molecular self-assembling fibrils that respond to external mechanical force by transforming from a macroscopically disorder state to a highly ordered uniaxial aligned state. The incorporation of aromatic-containing amino acids and negatively charged amino acids lead to self-assembly motifs that transform into uniform nanofibrils in acidic solution. Adjusting the pH level of aqueous solution introduces optimal negative charge to the surface of self-assembling nanofibrils inducing long-range electrostatic repulsion forming a nematic phase. Upon external mechanical force, nanofibrils align in the force direction. Via evaporation casting in capillary confinement, the solvated synthetic self-assembling nanofibrils transform into scalable lamellar domains. Adjusting capillary geometry and drying procedure offers further parameters for tuning the mesoscale alignment of nanofibrils generating a variety of interference colors. The design paradigm of mechanoresponsive alignment of self-assembled nanofibrils as an addition of nanofabrication techniques is potentially employable for realizing biomimetic optical structures.

Nanolubrication in deep eutectic solvents.

We report surface force balance measurements of the normal surface force and friction between two mica surfaces separated by a nanofilm of the deep eutectic solvent ethaline. Ethaline, a 1 : 2 mixture of choline chloride and ethylene glycol, was studied under dry conditions, under ambient conditions and with added water, revealing surface structural layers and quantised frictional response highly sensitive to water content, including regions of super-lubric behaviour under dry conditions and with added water. We also report exceptionally long-ranged electrostatic repulsion far in excess of that predicted by Debye-Hückel theory for a system with such high electrolyte content, consistent with previously reported observations of "underscreening" in ionic liquid and concentrated aqueous electrolyte systems [Smith et al., J. Phys. Chem. Lett., 2016, 7(12), 2157].

Fibril Charge Affects α-Synuclein Hydrogel Rheological Properties.

In this paper, we have investigated the interactions between α-synuclein fibrils at different pH values and how this relates to hydrogel formation and gel properties. Using a combination of rheology, small-angle X-ray scattering, Raman spectroscopy, and cryo-transmission electron microscopy (cryo-TEM) experiments, we have been able to investigate the relationship between protein net charge, fibril-fibril interactions, and hydrogel properties, and have explored the potential for α-synuclein to form hydrogels at various conditions. We have found that α-synuclein can form hydrogels at lower concentrations (50-300 μM) and over a wider pH range (6.0-7.5) than previously reported. Over this pH range and at 300 μM, the fibril network is electrostatically stabilized. Decreasing the pH to 5.5 results in the precipitation of fibrils. A maximum in gel stiffness was observed at pH 6.5 (∼1300 Pa), which indicates that significant attractive interactions operate at this pH and cause an increase in the density of hydrophobic contacts between the otherwise negatively charged fibrils. We conclude that fibril-fibril interactions under these conditions involve both long-range electrostatic repulsion and a short-range hydrophobic attractive (sticky) component. These results may provide a basis for potential applications and add to the understanding of amyloids.

Interplay between Short-Range Attraction and Long-Range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes.

In eukaryotic cells, ribonucleoproteins (RNPs) form mesoscale condensates by liquid-liquid phase separation that play essential roles in subcellular dynamic compartmentalization. The formation and dissolution of many RNP condensates are finely dependent on the RNA-to-RNP ratio, giving rise to a windowlike phase separation behavior. This is commonly referred to as reentrant liquid condensation (RLC). Here, using ribonucleoprotein-inspired polypeptides with low-complexity RNA-binding sequences as well as an archetypal disordered RNP, fused in sarcoma, as model systems, we investigate the molecular driving forces underlying this nonmonotonous phase transition. We show that an interplay between short-range cation-π attractions and long-range electrostatic forces governs the heterotypic RLC behavior of RNP-RNA complexes. Short-range attractions, which can be encoded by both polypeptide chain primary sequence and nucleic acid base sequence, control the two-phase coexistence regime, regulate material properties of polypeptide-RNA condensates, and oppose condensate reentrant dissolution. In the presence of excess RNA, a competition between short-range attraction and long-range electrostatic repulsion drives the formation of a colloidlike cluster phase. With increasing short-range attraction, the fluid dynamics of the cluster phase is arrested, leading to the formation of a colloidal gel. Our results reveal that phase behavior, supramolecular organization, and material states of RNP-RNA assemblies are controlled by a dynamic interplay between molecular interactions at different length scales.

Molecular Energetics of Doxorubicin Pumping by Human P-Glycoprotein.

The pumping of antitumor drugs by P-glycoprotein (P-gp) causes multidrug resistance (MDR) and consequent failure of chemotherapy. However, the understanding on the molecular mechanism of P-gp for transporting substrates is still far from adequate. Herein, the transport of a typical antitumor drug, doxorubicin, by P-gp is investigated using targeted molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The MM-PBSA analysis identifies the driving forces for the transport of doxorubicin toward the extracellular space as electrostatic repulsions in the initial stage, which are contributed by positively charged residues (R148, K181, K189, K285, K291, K734, R789, K826, K934, and K1000) and then hydrophobic interactions provided by hydrophobic residues (L65, M69, F336, I340, F343, Y953, V982, F983, and M986). The contributions of these residues are further validated by targeted MD simulations, which shows blocked pumping after the mutation of these important residues to glycine. The MM-PBSA and minimum distance analyses of each residue during the transport reveal that the positively charged residues promote the transport of doxorubicin through long-range electrostatic repulsions and the hydrophobic residues provide a pathway through continuous hydrophobic interactions to maintain the transport. The results have thus provided molecular insights into the function of P-gp and would be beneficial in the design of potent P-gp inhibitors against MDR in the medication of cancers.

Carbon Nanotube and Cellulose Nanocrystal Hybrid Films

The use of cellulose nanocrystals (CNC) in high performance coatings is attractive for micro-scale structures or device fabrication due to the anisotropic geometry, however CNC are insulating materials. Carbon nanotubes (CNT) are also rod-shaped nanomaterials that display high mechanical strength and electrical conductivity. The hydrophobic regions of surface-modified CNC can interact with hydrophobic CNT and aid in association between the two anisotropic nanomaterials. The long-range electrostatic repulsion of CNC plays a role in forming a stable CNT and CNC mixture dispersion in water, which is integral to forming a uniform hybrid film. At concentrations favorable for film formation, the multiwalled nanotubes + CNC mixture dispersion shows cellular network formation, indicating local phase separation, while the single-walled nanotube + CNC mixture dispersion shows schlieren texture, indicating liquid crystal mixture formation. Conductive CNT + CNC hybrid films (5–20 μm thick) were cast on glass microscope slides with and without shear by blade coating. The CNT + CNC hybrid films electrical conductivity increased with increasing CNT loadings and some anisotropy was observed with the sheared hybrid films, although to a lesser extent than what was anticipated. Percolation models were applied to model the hybrid film conductivity and correlate with the hybrid film microstructure.